This application is being submitted in response to NIH-RFA-DK-02-013. The purpose of the application is to apply for the Central Office of the Southwest Pediatric Nephrology Group (SPNSG) to be chosen as one of the four Regional Centers in the nationwide randomized clinical trial (RCT) of treatment options for children and young adults with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). The SPNSG has been responsible for coordinating multicenter clinical trials in children with kidney disease for twenty (20) years, and for the past six (6) years in adults with IgA Nephropathy. We are currently conducting a multicenter trial evaluating the efficacy of mycophenolate mofetil in children with steroid dependent nephrotic syndrome and we are starting a new RCT in patients with IgA Nephropathy who are aged 7 to 70 years of age. The location of our center and the experience we have had in developing networks for multicenter studies, will allow us to be a very effective site for conducting the study for patients and physicians in the Southwest and Midwest regions of the United States. The specifics of the proposal provide one approach to the RCT that is being designed and, as requested in the RFA, provides details regarding our approach to patient and center recruitment. The specific region of the U.S.A. that we propose to cover encompasses the major Nephrology Centers in fourteen (14) states: Texas, Louisiana, Oklahoma, Arkansas, Kansas, Tennessee, Mississippi, Missouri, Colorado, Arizona, Illinois, Utah, New Mexico and Kentucky. The trial that we are proposing involves a placebo-controlled evaluation of two immunomodulating drugs (cyclosporine A and mycophenolate mofetil) for the treatment of FSGS in a large group of children and adults less than 40 years of age. All of the patients (including the "placebo" group) will receive an angiotensin converting enzyme inhibitor (enalapril)-which we consider to be standard care of therapy. The patients will be treated for 2 years during which we will be measuring their urinary protein levels as a marker of kidney disease. These measurements will be continued for an additional six months after the 2-year course of therapy has been completed. Our ultimate goal with the treatments proposed is to enable the patients to preserve their kidney function and avoid the need for subsequent kidney transplantation.